Fenofibrate Combined With Ursodeoxycholic Acid in Subjects With Primary Biliary Cholangitis

Phase 3RecruitingNCT05751967

Xijing Hospital of Digestive Diseases150 enrolled

Overview

Current treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier. Recently, our team designed and validated a new early criterion for distinguishing high-risk PBC patients in a Chinese population for the first time. Our data indicated that PBC patients with ALP ≤ 2.5 × ULN, AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi'an criterion) after 1 month UDCA treatment were likely to have better prognosis. It can be readily applied in the rapid identification of PBC patients who require additional therapeutic approaches. However, whether it is reasonable to apply it to the response definition of clinical research, and the guidance of PBC management and choice of second-line treatment, further research is needed.

This is a multi-center, randomized, placebo-controlled, parallel-group study that will assess the efficacy and safety of fenofibrate in patients with PBC who had an inadequate biochemical response to UDCA, as defined by the Xi'an criteria. Fenofibrate or placebo 200 mg will be daily administered in combination with UDCA 13-15 mg/kg/d for 48 months. Patient safety will be monitored. Primary end-point will be the percentage of patients with a complete normalization of the ALP and TBIL. Secondary endpoints will include the percentage of drug-related adverse events, survival rates without liver transplantation or liver decompensation, time course of non-invasive liver fibrosis measurements (LSM), time course of endoscopic, ultrasound, and biochemical features of portal hypertension, time course of pruritus and of quality of life using validated scales.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Must have provided written informed consent; * Age 18-75 years; * BMI 17-28 kg/m2 * Male or female with a diagnosis of PBC, by at least two of the following criteria: * History of AP above ULN for at least six months; * Positive AMA titers (\>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies; * Documented liver biopsy result consistent with PBC. * Incomplete response to UDCA defined by Xi'an criteria (ALP \>2.5× ULN, AST\>2×ULN or TBIL\>1×ULN) after UDCA treatment for 4-6 weeks with at least one abnormal test in ALP or TBIL. Exclusion Criteria: * History or presence of other concomitant liver diseases. * ALT/AST \> 5×ULN, TBIL \> 3×ULN. * If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating. * Allergic to fenofibrate or ursodeoxycholic acid. * Taking hepatotoxic drugs (e.g., dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) for more than 2 weeks within 6 months, and long-term hormonal users. * Recurrent variceal bleeding, poorly controlled hepatic encephalopathy or refractory ascites. * Patients with a history of severe cardiac, cerebrovascular, renal, respiratory disease or functional failure, and psychiatric disorders (including those due to alcohol and drug abuse). * Creatinine \>1.5×ULN and creatinine clearance \<60 ml/min. * Currently using statins (such as pravastatin, fluvastatin, and simvastatin), other fibrates (such as gemfibrozil and bezafibrate), and drugs structurally similar to fenofibrate (like ketoprofen). * Planned to receive an organ transplant or an organ transplant recipient. * Needing Liver transplantation within 1 year according to the Mayo Rick score. * Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Investigator.

Locations (7)

The second hospital of Lanzhou University

Lanzhou, Gansu, China

RECRUITING

Sun Yat-sen Memorial Hospital

Guangzhou, Guangdong, China

NOT_YET_RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, China

RECRUITING

Ying han

Xi'an, Shaanxi, China

RECRUITING

Sichuan Provincial People's Hospital,

Chengdu, Sichuan, China

RECRUITING

Tianjin Medical University General Hospital

Tianjin, China

RECRUITING

Outcomes

Primary Outcomes

Percentage of patients with complete biochemical response

The normalisation of Alkaline Phosphatase (ALP) and total bilirubin (TBIL).

Time frame: 48 weeks

Secondary Outcomes

Percentage of patients having complete biochemical response

The normalisation of Alkaline Phosphatase (ALP) and total bilirubin (TBIL) at 4, 12, 24, and 36 weeks.

Time frame: 4, 12, 24, 36, and 48 weeks

Assessment of the fatigue and the quality of life

Change from baseline in primary biliary cholangitis -40 (PBC-40) quality of life (QoL) questionnaire scores.

Time frame: 4, 12, 24, 36, and 48 weeks

Assessment of the fatigue and the quality of life

Change from baseline in pruritus as assessed by Visual Analogue Scale (VAS) total score for fatigue and pruritus.

Time frame: 4, 12, 24, 36, and 48 weeks

Evolution of the biological markers of the hepatic function or being in the usual prognostic scores

Mayo score at 4, 12, 24, 36, and 48 weeks

Time frame: 4, 12, 24, 36, and 48 weeks

Evolution of the biological markers of the hepatic function or being in the usual prognostic scores

Child-Puch score at 4, 12, 24, 36, and 48 weeks

Time frame: 4, 12, 24, 36, and 48 weeks

Evolution of the biological markers of the hepatic function or being in the usual prognostic scores

MELD score at 4, 12, 24, 36, and 48 weeks

Time frame: 4, 12, 24, 36, and 48 weeks

Evolution of the biological markers of the hepatic function or being in the usual prognostic scores

GLOBE-PBC score at 48 weeks

Time frame: 48 weeks

Evolution of the biological markers of the hepatic function or being in the usual prognostic scores

UK-PBC score at 48 weeks

Time frame: 48 weeks

Percentage of patients having biological or clinical adverse events

Increase of creatinine

Time frame: 4, 12, 24, 36, and 48 weeks

Percentage of patients having biological or clinical adverse events

Increase of Blood urea nitrogen

Time frame: 4, 12, 24, 36, and 48 weeks

Percentage of patients having biological or clinical adverse events

Increase of creatine kinase

Time frame: 4, 12, 24, 36, and 48 weeks

Percentage of patients having biological or clinical adverse events

Increase of ALT and AST.

Time frame: 4, 12, 24, 36, and 48 weeks

Survival without transplantation and hepatic impairment

Occurrence of ascites, variceal bleeding, hepatic encephalopathy, liver-transplantation, or death.

Time frame: 48 weeks

Fenofibrate Combined With Ursodeoxycholic Acid in Subjects With Primary Biliary Cholangitis

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts